This program requests 5 predoctoral and 1 postdoctoral positions for training in immune system development and regulation (ISDR). The program has expanded to 28 trainers with expertise in the development and regulation of immune system, which are a subset of the Immunology Graduate Group (IGG) faculty at the University of Pennsylvania. The IGG at Penn is a discipline-based graduate training program and, as the first in the country to offer a degree in Immunology, has a >30-year record of outstanding training. The academic elements of the IGG curriculum form the core experiences for trainees in the proposed ISDR program, and reflect a proven mixture of coursework, laboratory rotations, research presentations, and thesis research. These are enriched by a large array of additional activities that foster scientific exchange and discussion, including ongoing activities such as our annual retreat and weekly immunology colloquium, as well as an agreement that affords training experiences with distinguished adjunct faculty on the NIH Bethesda campus. The assembled trainers for this grant have extensive and highly productive training records in the area of immune system development and regulation, as well as substantial research support to assure quality and continuity of the training experience. The breadth and strength of the assembled training faculty affords a diverse array of potential trainee mentors. The Immunology Predoctoral program has over 100 applicants annually, which are a subset of over 1,000 applicants to biomedical graduate studies at the University of Pennsylvania School of Medicine. The Immunology program recruits between 8 to 12 PhD and 2 to 5 MD-PhD trainees per year, yielding a student body of ~60 students. This program focuses specifically on students/faculty whose research is directed towards understanding the development and regulation of the immune system and immune responses. In this regard, the ISDR fosters research and research training that bear directly on control and manipulation of the immune system in health and disease.